This application is built on the hypothesis that coordinated changes in the expression of specific MMPs and their inhibitors produce alterations in the fetal membranes that lead to their rupture under normal and pathological conditions. Aim 1 is to characterize amnion type I and type IV collagen fragmentation patterns. Aim 2 is to determine if mutations in collagen chains affect the structural dissolution of the amnion at term. Aim 3 is to define the temporal and spatial patterns of expression of MMPs capable of degrading interstitial and type IV collagens in the rat amnion. Aim 4 is to determine if MMP inhibitors and antisense oligonucleotides directed against specific MMPs prevent structural changes in the amnion. Aim 5 is to determine if the induction of MMPs and changes in the amnion are dependent on gestational age. Aim 6 is to determine if withdrawal of progesterone induces MMP activities and the terminal changes in amnion structure. Aim 7 is to identify amnion-specific genes.